Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

July 18, 2013 updated by: UNICANCER

Randomized And Multicentric Opened Phase III Study Evaluating The Concomitant Administration Of Docetaxel 75MG/M2 and Epirubicine 75MG/M2 Versus FEC 100 In Non Metastatic With Positive Lymphatic Nodes Breast Cancer Subjects, And The Sequential Addition Of Herceptin In (HER2+++) And (HER2++ And FISH+) Subjects

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more effective in treating breast cancer.

PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus radiation therapy with or without trastuzumab in treating women who have breast cancer that has spread to lymph nodes in the axilla (under the arm).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion.
  • Determine survival of patients treated with these regimens.
  • Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens.
  • Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors.
  • Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts.

  • Part I: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.
    • Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I.

Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment.

Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years.

  • Part II: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year.
    • Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.

Study Type

Interventional

Enrollment (Actual)

3010

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49036
        • Centre Paul Papin
      • Annecy, France, 74011 Cedex
        • Centre Hospitalier D'annecy
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Bourg En Bresse, France, 01012
        • C.H. Bourg En Bresse
      • Caen, France, 14076
        • Centre Regional Francois Baclesse
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Creteil, France, 94010
        • Hôpital Intercommunal de Créteil
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Grenoble, France, 38100
        • Institut Prive de Cancerologie
      • Harfleur, France, 76700
        • Clinique du Petit Colmouilins
      • Lagny Sur Marne, France, 77405
        • Centre Hospitalier de Lagny
      • Le Chesnay, France, 78157
        • Hôpital André Mignot
      • Le Havre, France, 76600
        • CMC Les Ormeaux
      • Marseille, France, 13273
        • Institut J. Paoli and I. Calmettes
      • Metz, France, 57038
        • Centre Hospitalier Regional Metz Thionville
      • Montbeliard, France, 25209
        • Centre Hospitalier General Andre Boulloche
      • Montpellier, France, 34298
        • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
      • Mulhouse, France, 68051
        • Centre Hospitalier de Mulhouse
      • Nantes-Saint Herblain, France, 44805
        • Centre Regional Rene Gauducheau
      • Paris, France, 75674
        • Hôpital Avicenne
      • Perpignan, France
        • Clinique Saint - Pierre
      • Poitiers, France, 86021
        • CHU Poitiers
      • Reims, France, 51056
        • Institut Jean Godinot
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Sainte Clotilde, France, 97492
        • Clinique Sainte Clotilde
      • Strasbourg, France, 67065
        • Centre Paul Strauss
      • Strasbourg, France, 67091
        • Hopitaux Universitaire de Strasbourg
      • Toulouse, France, 31052
        • Institut Claudius Regaud
      • Villejuif, France, F-94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast

    • Axillary lymph node invasion (N1, N2, or N3)
    • No cutaneous invasion
    • No T4a or greater disease
  • No clinically or radiologically suspected metastases
  • No clinically or radiologically suspected contralateral lesion
  • No deeply adherent or inflammatory disease
  • Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days
  • No prior breast cancer

  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 to 64

Sex

  • Female

Menopausal status

  • Not specified

Performance status

  • WHO 0-1

Life expectancy

  • Not specified

Hematopoietic

  • WBC at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • ALT and AST no greater than 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2.5 times ULN
  • Bilirubin no greater than ULN
  • Hepatitis B and hepatitis C negative
  • No hepatic dysfunction

Renal

  • Creatinine less than 1.3 mg/dL OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular

  • ECHO normal
  • LVEF at least 50%

Pulmonary

  • FEV normal
  • No dyspnea at rest
  • No supplemental oxygen dependence

Other

  • Not pregnant
  • Fertile patients must use effective contraception
  • HIV negative
  • No active infection
  • No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
  • No contraindication to anthracycline therapy
  • No chronic medical or psychological condition
  • No geographic or social reason that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • At least 4 weeks since prior chemotherapy
  • No other concurrent chemotherapy
  • No contraindication to anthracycline therapy

Endocrine therapy

  • No prior hormonal therapy

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics

Other

  • At least 4 weeks since prior experimental therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 6 FEC
Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.
Biological: Trastuzumab
8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)
Other Names:
  • Herceptin
Drug: Cyclophosphamide
500 mg/m², D1 and every 3 weeks
Drug: Epirubicin
100 mg/m², D1 and every 3 weeks
Other Names:
  • epirubicin hydrochloride
Drug: Fluorouracil
500 mg/m², D1 and every 3 weeks
Experimental: 6 DE
Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I
Biological: Trastuzumab
8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)
Other Names:
  • Herceptin
Drug: Epirubicin
100 mg/m², D1 and every 3 weeks
Other Names:
  • epirubicin hydrochloride
Drug: docetaxel
on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival
Time Frame: 5 years from randomization
5 years from randomization

Secondary Outcome Measures

Outcome Measure
Time Frame
Herceptin safety
Time Frame: 5 years from randomization
5 years from randomization
Overall survival
Time Frame: 5 years from randomization
5 years from randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Investigators

  • Study Chair: Marc Spielmann, MD, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2001

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

February 5, 2003

First Submitted That Met QC Criteria

February 5, 2003

First Posted (Estimate)

February 6, 2003

Study Record Updates

Last Update Posted (Estimate)

July 19, 2013

Last Update Submitted That Met QC Criteria

July 18, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-0140/0005 - PACS 04
  • FRE-FNCLCC-PACS-04/0005
  • EU-20236
  • PACS04 (Other Identifier: UNICANCER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Trastuzumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malta

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe